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Abstract Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) has potential benefits compared to conventional Cardiopulmonary Resuscitation (CCPR) in children. Although no randomised trials for paediatric ECPR have been conducted, there is extensive literature on survival, neurological outcome and risk factors for survival. Based on current literature and guidelines, we suggest recommendations for deployment of paediatric ECPR emphasising the requirement for protocols, training, and timely intervention to enhance patient outcomes. Factors related to outcomes of paediatric ECPR include initial underlying rhythm, CCPR duration, quality of CCPR, medications during CCPR, cannulation site, acidosis and renal dysfunction. Based on current evidence and experience, we provide an approach to patient selection, ECMO initiation and management in ECPR regarding blood and sweep flow settings, unloading of the left ventricle, diagnostics whilst on ECMO, temperature targets, neuromonitoring as well as suggested weaning and decannulation strategies., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A Hoskote, M Davidson and PP Roeleveld are all members of the EuroELSO steering committee. (no financial interests).

Aim: To evaluate the use of computed tomography (CT) and low-dose CT in the detection of latent tuberculosis (TB)., Materials and Methods: A systematic search of literature in adherence with the PRISMA guidelines was carried out. Quality assessment of the included studies was conducted., Results: The search strategy identified a total of 4,621 studies. Sixteen studies were considered eligible and included in the review. There was high heterogeneity among all studies. CT was identified as much more sensitive for the detection of latent TB in all studies despite chest radiography often being recommended in guidelines to assess patients for latent TB. Low-dose CT showed promising results in four of the studies; however, these results were limited due to small sample sizes., Conclusion: CT is much superior to chest radiography consistently identifying additional cases of latent TB. There are limited high-quality publications available using low-dose CT but findings thus far suggest low-dose CT could be used as an alternative to standard-dose CT for the detection of latent TB. It is recommended that a randomised controlled trial investigating low-dose CT should be carried out., (Copyright © 2023. Published by Elsevier Ltd.)

Aim Physical Activity (PA) and Mindfulness-Based Stress Reduction (MBSR) both have positive effects on medical student well-being. The 'MED-WELL' programme is a curricular intervention that combines PA and education on exercise as medicine. This trial evaluates whether there is a mean difference in outcomes of participants of an exercise intervention, the 'MED-WELL' programme, versus a control group which engages in a MBSR programme. Methods All second-year medical students were voluntarily allocated into the intervention or control group. Data on overall health and well-being, sleep quality, loneliness, current level of PA, and confidence in prescribing exercise as medicine was analysed from both groups at baseline and after eight weeks. Results Within groups the intervention and control groups showed statistically significant improvements in overall well-being (p=0.010, p=0.005 respectively) and in sleep quality (p<0.001, p=0.007 respectively). The intervention group had statistically significant improvements in levels of PA (p=0.003) and confidence in prescribing exercise (p<0.001). However, there were no statistically significant differences in changes in outcome measures between groups. Conclusion This study has shown that participants in an exercise intervention, the 'MED-WELL' programme, had similar improvements in overall wellbeing and sleep quality to those in a control group who participated in a MBSR programme of the same duration., Competing Interests: All authors declare that they have no conflicts of interest.

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that primarily affects females, resulting in severe cognitive and physical disabilities, and is one of the most prevalent causes of intellectual disability in females. More than fifty years after the first publication on Rett syndrome, and almost two decades since the first report linking RTT to the MECP2 gene, the research community's effort is focused on obtaining a better understanding of the genetics and the complex biology of RTT and Rett-like phenotypes without MECP2 mutations. Herein, we review the current molecular genetic studies, which investigate the genetic causes of RTT or Rett-like phenotypes which overlap with other genetic disorders and document the swift evolution of the techniques and methodologies employed. This review also underlines the clinical and genetic heterogeneity of the Rett syndrome spectrum and provides an overview of the RTT-related genes described to date, many of which are involved in epigenetic gene regulation, neurotransmitter action or RNA transcription/translation. Finally, it discusses the importance of including both phenotypic and genetic diagnosis to provide proper genetic counselling from a patient's perspective and the appropriate treatment., Competing Interests: The authors declare no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Mucopolysaccharidosis type VI (MPS VI) is a progressive, autosomal, recessive lysosomal disorder. This disorder, due to a deficiency in N-acetylgalactosamine-4-sulfatase (ASB), results in an accumulation of glycosaminoglycan (GAG), causing multiple organ failures. In this study, monochorionic biamniotic twins with the severe form of MPS VI underwent enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (galsulfase) at 1 mg/kg. After 9 years of ERT, a comprehensive clinical examination was performed. Several types of biochemical, immunological, and genetic investigations were also conducted. Both twins showed the typical symptoms and signs of MPS VI at baseline, including short stature, progressive dysmorphic facial features, and dysostosis multiplex. Twin 2 presented stronger multisystemic involvement, with marked musculoskeletal, neurological, and odontological components. She also developed an ischemic spinal cord lesion after surgery, which is the first case described in the literature in Maroteaux-Lamy syndrome. However, the extent of disease was found to be equally stabilized in the two sisters, concretely the cardiac and respiratory functions and body length. The early diagnosis and treatment of MPS VI are critical for an optimal clinical outcome, and further evidence for the new treatment strategies is needed.

Breast cancer survivors are at risk of bone loss due to hormonal treatment. We conducted a case note audit to investigate patterns of care and adherence to guidelines for initial management of risk of bone loss in 42 women receiving hormonal therapy. All those receiving aromatase inhibitors (n = 14) and 10 on tamoxifen had a bone density assessment. Eleven (26%) women had osteopenia and four (9.5%) osteoporosis. Management was variable and not always aligned with the guidelines., (© 2015 Royal Australasian College of Physicians.)

Aim: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area., Methods: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage., Results: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional., Conclusion: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: CblC deficiency produces a combination of methylmalonic aciduria (MMA) and homocystinuria (HCU), and is the most common error of cobalamin metabolism. Patients present a wide spectrum of symptoms, ranging from early severe multisystemic forms, to milder late-onset phenotypes. Cognitive and visual impairment are nearly constant. Hydroxocobalamin (OHCbl), betaine, folinic acid, levocarnitine and eventually dietary protein restriction are the main therapeutic approaches. Although early introduction of OHCbl is crucial, no standardized protocols regarding dose adaptation exist. No reports on long-term outcomes after high doses of this vitamin have been published., Methods: In this study five patients with CblC deficiency (early severe forms) were treated with high doses of OHCbl for 18 to 30months. Clinical examinations, neurological assessment, and biochemical studies (plasma total homocysteine (tHcy), amino acids, hydroxocobalamin, and methylmalonic acid in urine) were periodically performed., Results: Variable clinical and biochemical outcomes were observed in patients treated with high doses of OHCbl. The best biochemical response was observed in those children with the worse metabolic control. By contrast, those patients with a concentration of tHcy around 50μmol/l or less showed only minor changes. Clinically, a considerable improvement was observed in those patients with severe problems in communication, expressive language and behavior., Conclusions: According to our study, high OHCbl doses in CblC deficiency could have a greater benefit in those children with a prior history of suboptimal metabolic control, and also in those with severe neurological phenotypes. More specifically, we observed improvements in communication skills and behavior. These results should encourage further prospective trials to determine the optimal OHCbl regimen and to generate protocols and guidelines in this rare disorder., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Personal health practices are important determinants of health. Smoking habits are well documented among doctors. However, alcohol consumption, exercise rates and obesity rates are not. No indigenous studies have been done in this area. This descriptive population study aims to determine these factors. A questionnaire was sent to 381 consultants in hospitals affiliated with UCC Medical School. The response rate was 52.5% (200/381). The smoking rate was 7.5% (15/200) and the alcohol consumption rate was 94% (188/200). Both were more prevalent in females. Over a fifth took no exercise and activity levels were similar between groups. Female consultants were better at weight management than males with a lower proportion over the healthy body mass index (BMI) level. The smoking rate and alcohol consumption rate is higher than other studies. When compared to the general population, doctors are a healthier weight and smoke less but more consultants drink and less exercise regularly.

Aims: The genes involved in choline transport and oxidation to glycine betaine in the biopesticidal bacterium Serratia entomophila were characterized, and the potential of osmoprotectants, coupled with increased NaCl concentrations, to improve the desiccation tolerance of this species was investigated., Methods and Results: Serratia entomophila carries sequences similar to the Escherichia coli betTIBA genes encoding a choline transporter and dehydrogenase, a betaine aldehyde dehydrogenase and a regulatory protein. Disruption of betA abolished the ability of Ser. entomophila to utilize choline as a carbon source. Quantitative reverse-transcriptase PCR analysis revealed that betA transcription was reduced compared to that of the upstream genes in the operon, and that NaCl and choline induced bet gene expression. Glycine betaine and choline increased the NaCl tolerance of Ser. entomophila, and osmotically preconditioned cultures survived better than control cultures following desiccation and immediately after application to agricultural soil., Conclusions: Addition of glycine betaine and NaCl to growth medium can greatly enhance the desiccation survival of Ser. entomophila, and its initial survival in soil., Significance and Impact of the Study: Serratia entomophila is sensitive to desiccation and does not persist under low soil moisture conditions. Techniques described here for enhancing the desiccation survival of Ser. entomophila can be used to improve formulations of this bacterium, and allow its application under a wider range of environmental conditions., (© 2012 AgResearch.)

Background: Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms., Methods: We report a case of a 67-year-old Caucasian woman, who was admitted with history of bleeding per rectum. We conducted a literature review of metachronous and synchronous multiple primary neoplasms., Results: Colonoscopy revealed a 3 cm tumour in the caecum and a small sigmoid tubulovillous polyp. Staging computed tomography showed a non-enhancing mass in the upper pole of the right kidney. Following a radical nephrectomy/right hemicolectomy, microscopy demonstrated a renal cell carcinoma. Follow-up colonoscopy visualised a mucosal irregularity at the site of the previous sigmoid polyp, with biopsies confirming invasive adenocarcinoma. Patient underwent a total colectomy with an ileo-rectal anastamosis., Conclusion: Multiple primary neoplasms are a well-recognised clinical entity. This report emphasises the need for a comprehensive evidence-based work-up in all cancer cases, especially when dealing with renal cell carcinoma, to look for coexisting metachronous/synchronous primary neoplasms.

Although few studies found that the offspring of women who experienced preeclampsia have higher blood pressure (BP) at childhood and adolescence, no study has observed whether this association exists for adult offspring. To examine whether maternal hypertensive disorder of pregnancy (HDP) predicts adult offspring BP. We followed a sub-sample of 2608 mother-offspring pairs for 21 years from an original cohort of 7223 singleton infants whose mothers gave birth in Brisbane, Australia between 1981 and 1983. HDP was defined as diastolic BP (DBP) over 90 mm Hg on at least two occasions beyond 20 weeks gestation associated with proteinuria and/or excessive fluid retention. Adult offspring's systolic BP (SBP) and DBP were measured at 21 years. Multivariable regressions were used to examine the independent associations of HDP with offspring BP. Unadjusted regression analysis showed that offspring of women who experienced HDP have 3.46 mm Hg greater SBP and 3.02 mm Hg greater DBP at 21 years. This association remained consistent after adjusting for potential confounding and mediating factors including offspring gender, age, percentile birth weight for gestation, placenta weight and body mass index (BMI) at 21 year, maternal age, education, racial origin, and smoking during pregnancy and their pre-pregnancy BMI. Findings of this study suggest that maternal HDP predicts adult offspring BP.

1. The objective of this work was to investigate the feasibility of head only waterbath stunning as a means of generating immediate and long lasting unconsciousness while preventing wing flapping and avoiding carcass damage. 2. EEG measurements showed that immersion of the heads of the broilers for one second in a waterbath containing water of conductivity 2 x 5 mS/cm and a 50 Hz electric field of 10 V/cm resulted in immediate unconsciousness, and that increasing the electric field strength extended the duration of unconsciousness. 3. The passage of a 25-30 mA alternating current of frequency 2000 Hz through the broilers' bodies suppressed the wing flapping that followed a stun. 4. When the body current and electric field were applied simultaneously, wing flapping was prevented and EEG signals were suppressed for over 30 seconds indicating that the immediate unconsciousness lasted long enough to facilitate humane slaughter.

Objective: Adults with non-affective psychosis show subtle deviations in a range of developmental trajectories as children and adolescents., Method: Based on a birth-cohort (n = 3801), we examined the Peabody Picture Vocabulary Test (PPTV) at age 5, and Raven's Standard Progressive Matrices (RSPM) and Wide Range Achievement Test reading scale (WRAT-R) at age 14. Items related to speech problems and attentional dysfunction were available from maternal- or self-report. At age 21, we identified 60 cohort members who were screen-positive for non-affective psychosis (SP-NAP)., Results: Impaired performance on the PPVT and RSPM (but not WRAT-R) predicted SP-NAP for males only. Male cohort members in the highest quartile for attentional dysfunction at ages 5 and 14 were about 5-8 times more likely to develop SP-NAP. SP-NAP in males was significantly associated with speech problems at age 14., Conclusion: Males who develop non-affective psychoses have subtle impairments in cognitive capacity prior to the development of their psychotic disorder.

Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient. All patients were categorized according to age at neurological disease onset, and were assessed using a standardized clinical assessment protocol: disability and cognitive function scales, positron emission tomography (PET), and biochemical markers. PET and disability scale evaluations indicated that cerebral hypometabolism and neurological symptoms were stabilized during treatment in juvenile-onset NP-C patients. EI and Li NP-C patients, who had higher disease severity at baseline (treatment start), showed increased disability scores and progressive cerebral hypometabolism during follow up. Similarly, while cognitive scale scores remained relatively stable in patients with juvenile NP-C, cognition deteriorated in EI and Li patients. Plasma chitotriosidase (ChT) activity was lower in the juvenile NP-C subgroup than in EI and Li patients, and generally increased in patients who discontinued treatment. Plasma CCL18/PARC and ChT activities indicated greater macrophagic activity in EI and Li patients versus juveniles. Miglustat was generally well tolerated; frequent adverse events included diarrhea and flatulence, which were managed effectively by dietary modification and loperamide. Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background: Patients' awareness of the increased cardiovascular risk associated with their diabetes is poorly documented., Aim: The aim of this study was to assess the awareness of diabetes complications among patients with diabetes in Ireland., Methods: Patients attending diabetes outpatient clinics in two teaching hospitals in different regions of the country were invited to complete a questionnaire., Results: A total of 258 (59.3% male) patients completed the questionnaire; mean age 57.8 years. On questioning, 53.5% reported cardiovascular disease as a potential complication of diabetes, with awareness rates of 61.2, 17.1, 16.3 and 12% for retinopathy, stroke, peripheral vascular disease and amputation, respectively. Disappointingly, less than half of respondents felt that improvements in diet and exercise could potentially reduce their cardiovascular risk., Conclusions: Awareness of cardiovascular risk and knowledge of effective measures to reduce this were low in our study and an alternative means of education may need to be considered.

Background: Birth cohort studies have shown that individuals who develop non-affective psychoses display subtle deviations in behaviour during childhood and adolescence. We had the opportunity to examine the widely used Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR) to explore the antecedents of non-affective psychosis., Method: Based on a birth cohort of 3801 young adults, psychopathology was assessed at years 5 and 14 using the CBCL and/or the YSR. Screen-positive non-affective psychosis (SP-NAP) was assessed at year 21 by using the Composite International Diagnostic Interview (CIDI) or a self-report checklist. The association between childhood symptoms and SP-NAP was examined using logistic regression., Results: Of the cohort, 60 subjects were classified as SP-NAP. In males, SP-NAP was associated with higher scores: (a) on year 5 CBCL 'Total', 'Aggression' and 'Social, Attention and Thought' scores; (b) on year 14 CBCL 'Social', 'Attention' and 'Delinquency' scores, and (c) YSR 'Total' and many YSR subscores. These associations were less clear for females. Hallucinations at year 14 were associated with SP-NAP for both sexes. Boys with high 'Total' scores at both years 5 and 14 were at greatest risk of SP-NAP (a 5-fold risk), followed by boys and girls whose 'Social, Attention and Thought' scores either increased or remained high from years 5 to 14 (3- to 13-fold risk)., Conclusions: Individuals who screen positive for non-affective psychosis show increased psychopathology during childhood and adolescence. The psychopathological trajectory of children who go on to develop schizophrenia anticipates the heterogeneity associated with the full clinical syndrome.

Objective: Objectives of this study were to examine the prospective association of childhood body mass index (BMI) and overweight and pubertal stages with BMI and overweight in early adulthood independent of each other., Design: A population-based prospective birth cohort., Subjects: We used a population-based prospective birth cohort of 2897 (52% men) young adults who were born during 1981-1983 in Brisbane, Australia, and for whom we had puberty stages using Tanner scale at 14 years and measured BMI at 5 years of age., Main Outcome Measures: Pubertal stages at adolescent and BMI and its categories at 21 years., Results: We found that increasing BMI and overweight at 5 years of age predict the advanced stages of puberty. An advanced stage of puberty predicts young adults' BMI and overweight status at 21 years. When taking both childhood BMI and pubertal status into consideration, we found that being overweight at 5 years substantively increases BMI at 21 years, regardless of the stage of puberty reported at 14 years. We also found that subjects with normal BMI at 5 years but with higher stages of puberty at 14 years had threefold greater risk to be overweight at 21 years compared with their counterparts. All associations remained consistent after controlling for potential confounders., Conclusions: Although this study underscores the impact of both child overweight and pubertal development on young adults' obesity, the mechanism that further explains the impact of puberty needs to be identified.

Objective: Psychotic-like experiences (PLE) in the general community are common. The aims of this study were to examine the prevalence and demographic correlates of PLE in young adults., Method: The sample consisted of 2441 subjects aged 18-23 years. Subjects completed the Composite International Diagnostic Interview (CIDI) and the 21-item Peters Delusional Inventory (PDI). Associations between age, gender, hallucinations and delusions were examined using logistic regression., Results: Both CIDI hallucinations and delusions predicted high scores on the PDI. Younger age was significantly associated with endorsement of CIDI delusions [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.48-0.92) and with PDI total scores (OR = 0.68, 95% CI 0.55-0.83). Women were significantly more likely to endorse items related to hallucinations (OR = 1.49, 95% CI 1.14-1.95) but not delusions., Conclusion: PLE are common in young adults. The mechanisms underpinning the age and gender gradients in PLE may provide clues to the pathogenesis of psychotic disorders.

Pompe disease results in the accumulation of lysosomal glycogen in multiple tissues due to a deficiency of acid alpha-glucosidase (GAA). Enzyme replacement therapy for Pompe disease was recently approved in Europe, the U.S., Canada, and Japan using a recombinant human GAA (Myozyme, alglucosidase alfa) produced in CHO cells (CHO-GAA). During the development of alglucosidase alfa, we examined the in vitro and in vivo properties of CHO cell-derived rhGAA, an rhGAA purified from the milk of transgenic rabbits, as well as an experimental version of rhGAA containing additional mannose-6-phosphate intended to facilitate muscle targeting. Biochemical analyses identified differences in rhGAA N-termini, glycosylation types and binding properties to several carbohydrate receptors. In a mouse model of Pompe disease, glycogen was more efficiently removed from the heart than from skeletal muscle for all enzymes, and overall, the CHO cell-derived rhGAA reduced glycogen to a greater extent than that observed with the other enzymes. The results of these preclinical studies, combined with biochemical characterization data for the three molecules described within, led to the selection of the CHO-GAA for clinical development and registration as the first approved therapy for Pompe disease.

Vanishing white matter disease (VWM) is one of the most frequent inherited childhood leukoencephalopathies. Five genes have been implicated in this disease ( EIF2B1-5), which encode the five subunits of translation initiation factor eIF2B. The disease has an autosomal recessive mode of inheritance. The age of onset and clinical severity vary widely. The diagnosis is based on magnetic resonance imaging (MRI) findings and is confirmed by molecular studies. We describe an affected female patient with a common and a novel mutation of the EIF2B5 gene, who demonstrated a progressive neurological and radiological deterioration. An unusual feature was her striking macrocephaly. She had an early clinical onset at two years of age and is currently still alive at 26 years of age.

1. The effectiveness of water bath electrical stunning of chickens with a constant root mean square (rms) current of 100 mA per bird delivered for 3 s using 100, 200, 400, 800 and 1500 Hz sine wave alternating current (AC) was investigated in layer hens. The quantitative changes occurring in the electroencephalogram (EEG) and somatosensory evoked potentials (SEPs) were used to determine the effectiveness of stunning. The changes occurring in the EEG were evaluated using Fast Fourier Transformations (FFT) and the SEPs were averaged to determine whether they were present or abolished. 2. The results of FFT indicated that stunning of chickens with a constant rms current of 100 mA per bird using 100 or 200 Hz induced epileptiform activity in all the hens, immediately followed by a reduction in the total (2 to 30 Hz) and relative (13 to 30 Hz) power contents in the EEG frequency bands indicative of unconsciousness and insensibility. The SEPs were abolished in the majority of hens stunned with 100 Hz and all the hens stunned with 200 Hz. 3. By contrast, stunning using 400, 800 or 1500 Hz failed to induce epileptiform activity in all the birds, the total and relative power contents in the EEG frequency bands showed a substantial increase, rather than reduction, and the SEPs were also retained in the majority of chickens. It is therefore suggested that stunning using these frequencies failed to stun them satisfactorily. In these birds, occurrence of a painful arousal, rather than unconsciousness, could not be ruled out. 4. It is therefore suggested that water bath electrical stunning of chickens with a minimum rms current of 100 mA per bird delivered using 100 or 200 Hz would be adequate to ensure bird welfare under commercial conditions, provided both the carotid arteries in the neck are severed at slaughter. On humanitarian and bird welfare grounds, a rms current of greater than 100 mA per bird should be applied whilst using frequencies of 400 Hz or more of sine wave AC for water bath electrical stunning of chickens.

This paper describes a model for the spatial spread of an epidemic in which the latent period has a Gamma distribution with arbitrary mean and variance while the infected and uninfected may have different diffusion coefficients. Using a variant of the "linear chain trick" we derive a simple algorithm for the propagation speed of the infection front. By way of verification, we show that, with suitably matched parameters, the algorithm agrees closely with speeds obtained numerically from the corresponding model in which the latent period is a constant.

The concept of a 'fail-safe' device to ensure that sufficient current is delivered to render a pig immediately unconscious when electrically stunned was investigated. For live pigs, no significant correlation could be determined between the pre-stun low voltage sensed impedance and the actual, higher voltage stun impedance. In contrast, a good correlation was found using heads from pigs killed more than 24 h previously. The impedance of a live pig's head was predominantly a function of the stunning voltage and decreased non-linearly with increasing voltage. The 'difference' between live and dead pigs was attributed to an 'ageing effect' which is not significant in the first few hours post mortem. No change in phase angle between corresponding stunning current and voltage waveforms, indicated that tissue reactance was not a contributing factor. It is concluded that 'fail-safe' devices based on low voltage pre-stun sensing are unlikely to meet the current legislative requirements (Council Directive 93/119/EC).

Objective: It is uncertain to what degree the relationship between breastfeeding and later cognitive development is a true biological effect, or is confounded by psychosocial factors. The study aim was to further investigate this relationship and the effect of duration of breast feeding on cognitive development., Methods: A total of 3880 children were followed from birth. Breastfeeding duration was measured by questionnaire at 6 months of age and a Peabody Picture Vocabulary Test Revised (PPVT-R) was administered at 5 years. PPVT-R scores were adjusted for the effects of a large array of biological and psychosocial confounders. The relationship between breastfeeding and the mean PPVT-R scores were examined using analysis of variance and multiple linear regression., Results: A strong positive relationship was demonstrated between breastfeeding and the PPVT-R scores with increasing scores with increased duration of breastfeeding. After adjusting for a wide range of biological and social factors, the adjusted mean for those breastfed for 6 months or more was 8.2 points higher for females and 5.8 points for males when compared to those never breastfed., Conclusion: These findings suggest a significant benefit to child development is conferred by breastfeeding and is related independently to longer periods of breastfeeding.

In March 1995, a mass mortality of pilchard started to occur in South Australia. This spread very rapidly throughout the Australian pilchard's range, later reaching New Zealand. In November 1998, a similar mass mortality broke out in South Australia and also spread, at a slower rate, throughout the Australian range. The mortality appeared to be caused by a herpesvirus. The mortality spread as a classical epidemic front, but its speed of progress and the brief duration of mortalities at a given location are extreme. We apply simple epidemic modelling techniques, SIR and SEIR modelling, to examine the factors behind the spread of this mortality and the differences between the 1995 and 1998/9 epidemics. We discuss biological factors influencing the critical processes of long-distance (D) and local (beta) transmission of infection.

1. Two separate experiments were carried out in this study. In experiment 1, the effectiveness of stunning broilers, as determined from physical responses, with a 6 mm diameter bolt and an air line pressure of 827 kPa, when fired at 90 degrees (perpendicular to the skull) 110 degrees, 120 degrees and 130 degrees (leaning towards beak) was evaluated. 2. In experiment 2, the effects of perpendicular shooting with two bolt diameters (3 and 6 mm) and two air line pressures (620 and 827 kPa) on spontaneous behaviour, electroencephalogram (EEG) and visually evoked potentials (VEPs) were evaluated in broilers. 3. Only the perpendicular shooting was effective in stunning/killing broilers (n= 10) as indicated by the immediate cessation of breathing and loss of neck muscle tension and eye reflexes. Deviations from the perpendicular shooting failed to stun 5 out of 9 broilers. The perpendicular vs non-perpendicular effect was significant. 4. Shooting broilers with a 3 mm bolt at air line pressures of 620 kPa (n=2) or 827 kPa (n=2) failed stun as indicated by the unaltered physical reflexes, EEG and VEPs. Shooting of two broilers with a 6 mm bolt at 620 kPa resulted in effective stunning and a very rapid recovery of consciousness in one bird and death in the other. 5. Captive bolt stunning of broilers with a 6 mm bolt and air line pressure of 827 kPa resulted in an immediate stun leading to death in all 6 broilers tested. In these broilers, a profound EEG suppression and abolition of VEPs occurred immediately after shooting. 6. It is suggested that the appropriate variables for captive bolt stunning of broilers are a minimum of 6 mm bolt diameter driven at an air line pressure of 827 kPa and a penetration depth of 10 mm.

Background: Previous research has indicated that there may be only a modest degree of agreement between different reporters of a child's behaviour (mental health). This raises the possibility that some descriptions of the child's behaviour may reflect the personal characteristics of the respondent. We examine two potential sources of bias that may influence reports of a child's behaviour/mental health. The first is the mental or emotional impairment of the respondent; the second concerns gender-related expectations of children., Methods: Mothers (and their children after the birth) were assessed at first clinic visit, 3-5 days after the birth, then 6 months, 5 years and 14 years after the birth. Some 70% of respondents giving birth remained in the study at the 14-year follow-up, leaving some 5277 cases for this analysis. At the 14-year follow-up, child behaviour (mental health) was assessed using the Child Behaviour Check List and the Youth Self Report. Maternal mental health was determined using the anxiety and depression subscales of the Delusions-Symptoms-States Inventory., Results: Mothers who were not emotionally impaired reported fewer child behaviour problems than did the children themselves. As the mother's current emotional impairment increased, so her reports of the child's behaviour problems increased, when compared with the child's own reports. Further, mothers attributed more internalising symptoms to female respondents, and more externalising symptoms to male respondents, than did the child respondents themselves., Conclusions: Mothers differ systematically from their children when they are reporting their child's behaviour (mental health). The more emotionally impaired the mother, the greater the degree to which she imputes the child to have behaviour problems. Further, female children are attributed to have more internalising behaviours and male children externalising behaviours.

Fabry disease results from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of the globotriaosylceramide (GL-3) and related glycosphingolipids, primarily in vascular endothelial lysosomes. Treatment is currently palliative, and affected patients generally die in their 40s or 50s. Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice demonstrated reduction of GL-3 in tissues and plasma, providing rationale for a phase 1/2 clinical trial. Here, we report a single-center, open-label, dose-ranging study of r-halphaGalA treatment in 15 patients, each of whom received five infusions at one of five dose regimens. Intravenously administered r-halphaGalA was cleared from the circulation in a dose-dependent manner, via both saturable and non-saturable pathways. Rapid and marked reductions in plasma and tissue GL-3 were observed biochemically, histologically, and/or ultrastructurally. Clearance of plasma GL-3 was dose-dependent. In patients with pre- and posttreatment biopsies, mean GL-3 content decreased 84% in liver (n=13), was markedly reduced in kidney in four of five patients, and after five doses was modestly lowered in the endomyocardium of four of seven patients. GL-3 deposits were cleared to near normal or were markedly reduced in the vascular endothelium of liver, skin, heart, and kidney, on the basis of light- and electron-microscopic evaluation. In addition, patients reported less pain, increased ability to sweat, and improved quality-of-life measures. Infusions were well tolerated; four patients experienced mild-to-moderate reactions, suggestive of hypersensitivity, that were managed conservatively. Of 15 patients, 8 (53%) developed IgG antibodies to r-halphaGalA; however, the antibodies were not neutralizing, as indicated by unchanged pharmacokinetic values for infusions 1 and 5. This study provides the basis for a phase 3 trial of enzyme-replacement therapy for Fabry disease.

1. Broiler chickens were killed using either an electrical waterbath (WB system) delivering 120 mA per bird (50 Hz, alternating current, AC) for 4 s or an alternative stun/kill method (ASK system); where head-only stunning for 1 s was immediately followed by head-to-body (vent) application for 1 s (150 mA, 50 Hz sine wave AC). Within each stun/kill system, the neck was cut ventrally or unilaterally 20, 60, or 180 s after killing. In addition, a control group of broilers was stunned with 100 mA per bird in a waterbath using 1500 Hz AC for 4 s and were bled by a ventral neck cut within 20 s. 2. Blood leaving the neck cut was collected for 90 s in a bin placed on an electronic balance and blood loss (g/kg body weight) calculated. 3. Individually identified, unplucked and uneviscerated carcases were held at ambient temperature until the end of the experimental day and then stored overnight in an air chiller (5 degrees C). The carcases were dissected and the incidence of broken furculum and coracoid bones, haemorrhaging in P. minor and P. major muscles, and discolouration of P. major muscles were determined. 4. When neck cutting was performed in broilers 20 s after the stun or kill, the ASK and WB systems, in comparison with high frequency stunning, produced on average about 10 g per kg less bleed out. Within the stun/kill systems, broilers killed by ASK had a greater bleed out than in the WB system. Neck cutting at 20 s or 60 s post-kill resulted in a greater bleed out than when performed after a delay of 180 s. Ventral or unilateral neck cutting resulted in a similar bleed out. 5. Stunning broilers with 1500 Hz AC resulted in lower incidences of broken bones, haemorrhaging in breast muscles and muscle discolouration post mortem than the stun/kill systems. These defects were significantly lower in the ASK than in the WB system. Delayed neck cutting increased the severity of discolouration occurring Post mortem in the breast muscles. 6. It is suggested that broilers killed by ASK can be neck cut with a delay of up to 180 s without compromising bleed out. The incidence of broken bones and haemorrhaging in breast muscles are significantly less with ASK than WB. 7. Owing to the commercial benefits and potential for improved welfare at slaughter, ASK would appear to be a better method than WB.

Objective: A number of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior., Method: This prospective, longitudinal study examines data on the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems., Results: Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths in reporting behavior problems appear to be related to the mothers' mental health., Conclusions: Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.

This study examines whether a small head circumference (HC) and low head-circumference growth velocity (HGV) during the first year of life predict consequences at school age in learning, cognition, and concentration. A total of 124 extremely-low-birthweight (ELBW) infants (birthweight 500 to 999 g) born between 1977 and 1986 were eligible for follow-up at the corrected ages of 4, 8, and 12 months and 2, 4, and 6 years. Infants were categorized as having a small HC (< 3% or 3 to 10%) on the basis of the 1990 British growth data which allowed standardized z-scores to be calculated for HC, independent of gestation and corrected age. HGV measurements were calculated using differences in the HC z-scores. In 1995, parents of 87 children agreed to participate in a study of learning and attention at school age. Attention-deficit-hyperactivity disorder (ADHD) was assessed using the Du Paul Rating Scale. Academic performances were based on a teacher questionnaire dealing with aspects of reading, writing, mathematics, and spelling. A child was considered to have a learning difficulty if academic problems were present in at least one of these four areas. Intellectual ability was assessed using the McCarthy Scale at 6 years. HC < 3% and 3 to 10% at 8 months' corrected age was strongly associated with school-aged learning problems (P=0.004), with a moderate specificity (70%), positive predictive value (PPV) (67%), and sensitivity (67%). HGV < or = 10% from birth to 4 months was also associated with learning problems at school age (P=0.01) with a higher specificity (98%) and PPV (88%) but lower sensitivity (20%). A logistic regression analysis was performed with the risk for learning difficulties at 8 months as the dependent variable. Sex, gestation, birthweight, multiple births, and a history of intraventricular hemorrhage did not substantially alter the unadjusted odds ratio (4.7; 95% CI 1.9 to 13.6). Maternal age and education did not confound the relation. No association was found between HC or HGV and ADHD. HC < 3% at 4 months (P<0.02), 8 months (P=0.02), and 12 months (P=0.04), and HGV between birth and 4 months (P<0.01) were significantly associated with low cognitive ability at 6 years.

1. The welfare and carcase quality implications of stunning/killing 7-week-old Japanese quail with either an electric current, 90% argon in air or a mixture of 30% carbon dioxide and 60% argon in air were investigated in 3 separate experiments. 2. The results showed that exposure of quail to either argon or the carbon dioxide-argon mixture resulted in loss of posture on average at 9 and 8 s respectively. In both gas mixtures, convulsions started 6 s after the loss of posture and the duration of clonic phase (wing flapping) did not differ significantly between the 2 gas mixtures. However, the duration of the tonic phase was found to be slightly longer with the carbon dioxide argon mixture than with argon alone (P<0.05). 3. The absence of a positive response to toe pinching performed soon after the loss of posture indicated that the birds became unconscious and insensible to pain before the onset of convulsions. 4. Carcase dissection showed that, in comparison with the electrical stunning, gas stunning/killing of quail in transport containers eliminated the problem of broken bones and significantly reduced haemorrhaging in breast and leg muscles.

Objective: Previous studies have linked maternal smoking during pregnancy with behavioral disturbance in children. However, additional evidence is needed to address the causality of the relationship. The present study analyses result from an Australian cohort of 5342 5-year-old children whose mothers were recruited early in pregnancy., Methods: Smoking history was gathered for prepregnancy, first clinic visit (FCV), late pregnancy, and when the child was 6 months and 5 years of age. Behavior problems at the age of 5 were assessed using a modified Child Behavior Check List (CBCL) shown to have high agreement with the complete CBCL. This resulted in the formation of three scales: internalizing; social, attentional and thought; and externalizing behavior problems, which were then dichotimized at the 90th percentile in each case. Logistic regression was used to model these outcomes as a function of maternal smoking at five time points during which it was assessed. A series of models explored the effect of additional adjustment for confounding. The predictors of attrition (29.5%) throughout the cohort were also identified by multivariate modeling., Results: The final analysis was carried out on a cohort of mother-child pairs for whom data and child behavior outcomes were complete. The mean age of children was 5 years, 6 months with a range from 4 to 6 years. The mean age of mothers at the time of birth of the child was 25 years, with a range from 13 to 47 years. Mothers lost to follow-up were more likely to be younger, single, and less well-educated than those who continued participation, although maternal smoking was not an independent determinant. Unadjusted analyses showed strong associations between externalizing child behavior and maternal smoking during pregnancy and at the 5-year follow-up, with relative risks (RRs) up to 2.6 for children of women smoking at least 20 cigarettes per day at the first antenatal clinic visit. A clear dose-response relationship existed in most relationships with higher levels of smoking being associated with higher rates of externalizing behavior problems. Weaker relationships occurred for internalizing behavior and social, attentional and thought behavior problems. Multivariate analysis of the timing in more detail that the association between maternal smoking and child behavior problems persisted, although the evidence for dose-response diminished. Moreover, it was primarily associated with smoking as determined by questions asked at the FCV (RR = 1.52, 2.03, 2.16) for 1 to 9, 10 to 19, and >/=20 cigarettes per day, respectively, compared with nonsmoking and secondarily by smoking determined at the 5-year follow-up (RR = 1.52, 1.87, 1.29) for 1 to 9, 10 to 19, and >/=20 cigarettes per day respectively, compared with nonsmoking. This association appeared to be independent of a wide range of possible confounders such as maternal age, education, social class, marital status and mental health, gestation at FCV, complications during pregnancy, the child's sex, gestational age at birth, and age at last follow-up. Adjustments were also made for the mother's employment since birth, family structure, and maternal mental health at the time of the CBCL assessment. Associations between externalizing behavior problems and maternal smoking at other times, and those between other behavioral problems examined and maternal smoking were not significant., Conclusion: Although previous studies have found evidence for an association between maternal smoking and child behavior problems, the strength of this study lies in its size, its detailed and consistent measurement of maternal smoking, and its ability to control for many social and biological factors linked to maternal smoking and child behavior. (ABSTRACT TRUNCATED)

Research suggests that cigarette use declines when women find out they are pregnant, increasing again after the birth. Pregnancy may provide many women with a substantial impetus to stopping smoking. Also, rates of smoking cessation and reduction may be class-related, with the highest socioeconomic-status groups manifesting higher rates of reduction. Using data from the Mater Hospital--University of Queensland Study of Pregnancy, we report family income related to rates of smoking before, during and after a pregnancy. Before becoming pregnant, 45.9 per cent of women in the sample were smokers. This declined to 34.7 per cent of women at their first clinic visit. Rates of heavy smoking (20 or more cigarettes per day) had returned to earlier levels by the six-month (after birth) follow-up. Women in the lowest family-income group had the highest rates of cigarette use before, during and after their pregnancy. Of the lowest family-income group, 8.4 per cent were heavy smokers before, during and after their pregnancy, compared with 2.8 per cent of women in the highest family-income group. Smoking cessation rates were highest in the highest family-income group (those who smoked least), but relapse rates after the birth were similar for all income groups. Arresting rates of smoking relapse by pregnant women should be seen as a major public health priority.

The study applies the principles behind the SERVQUAL model and uses Donabedian's framework to compare and contrast Malta's public and private hospital care service quality. Through the identification of 16 service quality indicators and the use of a Likert-type scale, two questionnaires were developed. The first questionnaire measured patient pre-admission expectations for public and private hospital service quality (in respect of one another). It also determined the weighted importance given to the different service quality indicators. The second questionnaire measured patient perceptions of provided service quality. Results showed that private hospitals are expected to offer a higher quality service, particularly in the "hotel services", but it was the public sector that was exceeding its patients' expectations by the wider margin. A number of implications for public and private hospital management and policy makers were identified.

Eight bacteriophages specific to Serratia entomophila, a commercially available bacterial pathogen of the New Zealand grass grub (Costelytra zealandica), were characterized by host range determination, morphology and restriction endonuclease patterns of DNA. Phages were originally isolated from grass grub larvae and fermenter broth where phages had disrupted large-scale production of S. entomophila. Seven of the phages (CW1-CW5, BC, and BT) had heads similar in size (approximately 60 x 60 nm) and long noncontractile tails (185 x 10 nm). Phage AgRP8 (P8) had a smaller head and a short tail structure. Restriction endonuclease analysis divided the phages into four groups: CW2, CW4, CW5, BC, and BT gave identical patterns, white CW1, CW3, and P8 each gave different patterns. Six distinct phage groups were distinguished by host range determination, after screening phages against 70 bacterial isolates: CW1, CW2/CW4, CW3, CW5, BC/BT, and P8. While confirming the indicated groupings by DNA analysis, it was possible to distinguish between some of the phages in the largest group: CW2/4 could be distinguished from CW5 and BC/BT. Screening of soil bacterial isolates of S. entomophila against nondiluted phages will aid in monitoring the establishment and persistence of strains applied for biological control of the grass grub.

Comminuted fractures of the middle phalanx have been well described in the horse. Choice of treatment, surgical planning and prognosis have traditionally been based upon evaluation of radiographs. However, the complex nature of comminuted fractures makes radiographic interpretation difficult. Computed tomography (CT) allows the production of cross-sectional images with spatial separation of structures which are superimposed on survey radiographs. This allows accurate assessment of the number and direction of fracture lines within the bone. In this paper we report the use of CT in the evaluation of 6 comminuted middle phalangeal fractures. Computed tomography is potentially useful in deciding the type of treatment, surgical planning and determining the prognosis.

Objective: This study examines the relationship between low family income (LFI) experienced at different points in time, chronic low income status and its impact on child behaviour measured at 5 years of age., Method: Longitudinal data from the Mater University Study of Pregnancy were used to measure LFI in families at three points in time (the antenatal period, 6 months post birth and at 5 years cf age). Outcome variables were three independent groups of behaviour problems labelled as externalising, social, attentional and thought (SAT) problems, and internalising problems. These groups were developed from the Child Behaviour Checklist. An analysis based on logistic regression modelling was carried out examining the relationship between LFI and a range of intermediate variables known to be associated with child behaviour problems., Results: The more often families experienced low income, the higher the rate of child behaviour problems at age 5. Low family income was still independently associated with SAT behaviour problems after controlling for smoking in the first trimester, parenting styles, maternal depression and marital dysharmony at age 5. The association between LFI and internalising and externalising behaviour problems was largely mediated by maternal depression., Conclusion: Low family income is a significant factor in the aetiology of a variety of child behaviour problems. The mechanisms involved in the link between LFI and childhood internalising and externalising behaviours involve the exposure of the children to maternal depression. However, the relationship between LFI and SAT behaviour problems remains to be elucidated.

Objective: In the context of substantial changes in family types and even family quality in recent times, this study is concerned with the extent to which family type and quality impacts on child behavior problems., Method: A sample of 8,556 pregnant women were enrolled in a prospective, longitudinal study. Details of changes in family type and family quality (assessed using Spanier Dyadic Adjustment Scale) were used to predict three second-order syndromes developed from the Child Behavior Checklist and administered to the mothers when the child was 5 years of age., Results: Mothers who experienced no partner changes (married and single) reported the lowest rates of child behavior problems for the three syndromes used in this study. In addition, mothers who more often described their relationship with their partner as poor also reported the highest rate of child behavior problems across all three syndromes. Adjustment for possible confounders did not alter these findings., Conclusion: Both changes of partner and dyadic conflict appear to lead to child behavior problems, with the latter factor appearing to have a greater impact than the former. Mothers who experienced no partner changes and no conflict appeared to have children with the fewest behavior problems.

Biological risk factors during intra-uterine life, delivery and the neonatal period, and measures of social adversity during pregnancy, were studied as predictors of a 'mildly impaired' (50 to 74) or 'borderline' (75 to 84) score on the Peabody Picture Vocabulary Test (PPVT) at aged five years in 3906 children. Biological risk factors in pregnancy were associated with neither PPVT outcome. Gestation of < 36 weeks, > 3 minutes to establishment of respiration and admission to intensive care were associated with a lower PPVT score indicating mild impairment, though only in the unadjusted analyses. A five minute Apgar score of < 5 and male sex were related to borderline scores, though only the latter remained significant after statistical allowance for possible confounding. In contrast, almost all measures of social adversity were related to both PPVT outcomes even after statistical adjustment for the influence of other factors.